Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.
NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.
Sprengel
R
R
Max-Planck Institute for Medical Research, Department of Molecular Neuroscience, Heidelberg, Germany.
Suchanek
B
B
Amico
C
C
Brusa
R
R
Burnashev
N
N
Rozov
A
A
Hvalby
O
O
Jensen
V
V
Paulsen
O
O
Andersen
P
P
Kim
J J
JJ
Thompson
R F
RF
Sun
W
W
Webster
L C
LC
Grant
S G
SG
Eilers
J
J
Konnerth
A
A
Li
J
J
McNamara
J O
JO
Seeburg
P H
PH
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons; D001921:Brain / Q000502:physiology*; D003213:Conditioning, Psychological; D019054:Evoked Potentials, Motor; D006624:Hippocampus / Q000502:physiology; D007696:Kindling, Neurologic / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009048:Motor Skills; D009419:Nerve Tissue Proteins / Q000032:analysis; D004856:Postural Balance; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D017384:Sequence Deletion; D009435:Synaptic Transmission
D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins